Facilitators of Motor Recovery Following Stroke

描述(由申请人提供)：在美国每年存活的350,000名中风患者中，约有200,000人患有持续性和致残性缺陷。卒中恢复的机制尚不清楚，因此现有的治疗干预措施处理不力。近年来，强制使用或强迫诱导治疗、药物治疗和细胞移植等调节疗法被用于卒中的康复；然而，这些疗法通常是在选定的慢性卒中受试者中进行研究的，并且这些干预的适当时机在很大程度上是未知的，并且在大多数情况下不是基于解剖或生理信息。在这个方案中，我们结合了脑成像技术，功能磁共振成像(FMRI)和电生理技术，经颅磁刺激(TMS)，来研究在活跃的恢复期损伤后解剖和生理过程是如何相互作用的，并确定它们对恢复的功能重要性。这种中风恢复的综合技术方法是这项建议最具创新性的方面，它允许我们收集单独使用每种技术无法获得的数据。在目前的文献中，有相互矛盾的证据表明，中风后，在运动恢复期间，同侧未受影响的感觉运动皮质及其未交叉的皮质脊髓束是否取代了对侧受影响的感觉运动皮质和/或皮质脊髓束的作用。在两个连续的实验中，我们建议使用fMRI和TMS相结合的方法来解决这个特定的问题，并检查中风后运动恢复的其他候选区域。我们的具体目标是，在实验1和实验2中，确定在临床定义的四个恢复阶段a)使用功能磁共振成像(FMRI)恢复运动的激活模式，并将其与b)ipsi和对侧皮质脊髓束的完整性以及使用TMS的皮质-皮质兴奋性的测量相关联，以确定用重复TMS(RTMS)抑制同侧感觉运动皮质的激活是否暂时影响恢复手的运动能力。我们假设，同侧运动皮质，虽然在恢复的手的运动时被激活，但是无功能的，可能会阻碍恢复，其他激活的皮质区域与恢复良好的手功能有关。确定运动网络中能够实现康复的关键区域和相互作用，以及在此期间它们变得重要的关键时间点，将指导现有治疗方法的应用和新的调制疗法的开发，以改善中风幸存者的预后并减少残疾。

DESCRIPTION (provided by applicant): Of the 350,000 people surviving stroke each year in the United States, approximately 200,000 have persistent and disabling deficits. The mechanisms of stroke recovery are unknown and therefore poorly manipulated by existing therapeutic interventions. Modulatory therapies such as forced-use or constraintinduced therapy, pharmaco-therapy, and cell transplantation have been employed in stroke recovery over recent years; however, these therapies are commonly investigated in selected groups of chronic stroke subjects and the appropriate timing for such interventions is largely unknown and in most cases is not based on anatomic or physiologic information. In this proposal, we combine a brain imaging technique, functional magnetic resonance imaging (fMRI), with an electrophysiological technique, transcranial magnetic stimulation (TMS), to investigate how the anatomical and physiological processes interact following injury during the active recovery period and to determine their functional importance for recovery. This combined technology approach to stroke recovery is the most innovative aspect of this proposal and it permits us to gather data unavailable by employing each technology alone. In the current literature there is contradictory evidence over whether following stroke, during motor recovery, the ipsilateral, unaffected, sensorimotor cortex and its uncrossed corticospinal tract take over the role of the contralateral, affected, sensorimotor cortex and/or corticospinal tract. In two sequential experiments we propose to use the combined fMRI and TMS approach to address this specific question and to examine other candidate regions in motor recovery following stroke. Our specific aims are, in experiment one, to determine at four clinically-defined stages of recovery a) the activation pattern of recovering movements using fMRI and correlate it to b) the integrity of ipsi- and contralateral corticospinal tracts and the measures of cortico-cortico excitability using TMS and in experiment 2, to determine whether inhibition of the ipsilateral sensorimotor cortex activation with repetitiveTMS (rTMS) temporarily affects motor performance in the recovering hand. We hypothesize that ipsilateral motor cortex, although activated on movement of the recovering hand, is non-functional and perhaps hinders recovery and that other activated cortical areas are associated with return of good hand function. Identifying the critical areas and interactions of the motor network that enable recovery and the critical timepoints during which they become important, will direct the application of existing, and the development of new modulatory therapies to improve outcome and reduce disabilities for stroke survivors.